2013
F1FO ATPase vesicle preparation and technique for performing patch clamp recordings of submitochondrial vesicle membranes.
Sacchetti S, Alavian KN, Lazrove E, Jonas EA. F1FO ATPase vesicle preparation and technique for performing patch clamp recordings of submitochondrial vesicle membranes. Journal Of Visualized Experiments 2013, e4394. PMID: 23685483, PMCID: PMC3676267, DOI: 10.3791/4394.Peer-Reviewed Original ResearchConceptsF1Fo-ATP synthaseATP synthaseF1Fo-ATPaseSubmitochondrial vesiclesNecrotic cell deathPro-apoptotic factorsCell deathOuter membraneBcl-2 family proteinsMitochondrial outer membraneImportant cellular functionsOuter membrane ruptureImportant mitochondrial functionsRole of mitochondriaMediation of signalsMitochondrial permeability transition poreProduction of ATPApoptotic cell deathPermeability transition poreInner membrane poreCellular functionsFamily proteinsInner membraneOxidative phosphorylationBeta subunit
2012
Effects of dexpramipexole on brain mitochondrial conductances and cellular bioenergetic efficiency
Alavian KN, Dworetzky SI, Bonanni L, Zhang P, Sacchetti S, Mariggio MA, Onofrj M, Thomas A, Li H, Mangold JE, Signore AP, DeMarco U, Demady DR, Nabili P, Lazrove E, Smith PJ, Gribkoff VK, Jonas EA. Effects of dexpramipexole on brain mitochondrial conductances and cellular bioenergetic efficiency. Brain Research 2012, 1446: 1-11. PMID: 22364637, PMCID: PMC3746080, DOI: 10.1016/j.brainres.2012.01.046.Peer-Reviewed Original ResearchMeSH KeywordsAdenosine TriphosphateAdrenergic beta-AntagonistsAnalysis of VarianceAnimalsBiophysical PhenomenaBrainCell SurvivalCells, CulturedCyclosporineDose-Response Relationship, DrugEnergy MetabolismEnzyme InhibitorsHumansMaleMembrane Potential, MitochondrialMiceMitochondriaMitochondrial MembranesNeuroblastomaNeuronsOligopeptidesOxygen ConsumptionPatch-Clamp TechniquesPropranololRatsRats, Sprague-DawleyConceptsAmyotrophic lateral sclerosisParkinson's diseaseRisk of deathChronic neurological disorderLateral sclerosisInefficient energy productionNeurological disordersMitochondrial dysfunctionMembrane currentsDiseaseCellular energy productionDysfunctional mitochondriaCellular stressSclerosisDysfunctionDexpramipexoleInjuryNeurons
2011
Bcl-xL regulates metabolic efficiency of neurons through interaction with the mitochondrial F1FO ATP synthase
Alavian KN, Li H, Collis L, Bonanni L, Zeng L, Sacchetti S, Lazrove E, Nabili P, Flaherty B, Graham M, Chen Y, Messerli SM, Mariggio MA, Rahner C, McNay E, Shore GC, Smith PJ, Hardwick JM, Jonas EA. Bcl-xL regulates metabolic efficiency of neurons through interaction with the mitochondrial F1FO ATP synthase. Nature Cell Biology 2011, 13: 1224-1233. PMID: 21926988, PMCID: PMC3186867, DOI: 10.1038/ncb2330.Peer-Reviewed Original ResearchMeSH KeywordsAdenosine TriphosphateAnimalsBcl-2 Homologous Antagonist-Killer ProteinBcl-2-Associated X ProteinBcl-X ProteinBiphenyl CompoundsCarbonyl Cyanide p-TrifluoromethoxyphenylhydrazoneCells, CulturedEnergy MetabolismEnzyme InhibitorsHippocampusHydrolysisMembrane Potential, MitochondrialMitochondriaMitochondrial MembranesMitochondrial Proton-Translocating ATPasesNeuronsNitrophenolsOligomycinsOxygen ConsumptionPatch-Clamp TechniquesPiperazinesProton IonophoresRatsRecombinant Fusion ProteinsRNA InterferenceSulfonamidesSynapsesTime FactorsTransfectionConceptsBcl-xLSynthase complexATP synthaseMitochondrial F1Fo-ATP synthaseAnti-apoptotic BCL2 family proteinsF1Fo-ATP synthaseATP synthase complexF1FO-ATPase activityBcl-xL activityATPase activityBcl-xL proteinBCL2 family proteinsEndogenous Bcl-xLPresence of ATPFamily proteinsATPase complexNormal neuronal functionMembrane leak conductanceSubmitochondrial vesiclesΒ-subunitProtect cellsGenetic inhibitionMitochondrial efficiencyF1FoApoptotic molecules
2007
Hypoxia increases BK channel activity in the inner mitochondrial membrane
Gu XQ, Siemen D, Parvez S, Cheng Y, Xue J, Zhou D, Sun X, Jonas EA, Haddad GG. Hypoxia increases BK channel activity in the inner mitochondrial membrane. Biochemical And Biophysical Research Communications 2007, 358: 311-316. PMID: 17481584, DOI: 10.1016/j.bbrc.2007.04.110.Peer-Reviewed Original Research
2006
Zinc-Dependent Multi-Conductance Channel Activity in Mitochondria Isolated from Ischemic Brain
Bonanni L, Chachar M, Jover-Mengual T, Li H, Jones A, Yokota H, Ofengeim D, Flannery RJ, Miyawaki T, Cho CH, Polster BM, Pypaert M, Hardwick JM, Sensi SL, Zukin RS, Jonas EA. Zinc-Dependent Multi-Conductance Channel Activity in Mitochondria Isolated from Ischemic Brain. Journal Of Neuroscience 2006, 26: 6851-6862. PMID: 16793892, PMCID: PMC4758341, DOI: 10.1523/jneurosci.5444-05.2006.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBlotting, WesternBrain IschemiaCaspasesChelating AgentsDiagnostic ImagingDose-Response Relationship, DrugEthylenediaminesIon Channel GatingIon ChannelsMaleMembrane PotentialsMicroscopy, Electron, TransmissionMitochondriaNADPatch-Clamp TechniquesRatsRats, Sprague-DawleySynaptosomesXanthenesZinc
2005
Actions of BAX on Mitochondrial Channel Activity and on Synaptic Transmission
Jonas EA, Hardwick JM, Kaczmarek LK. Actions of BAX on Mitochondrial Channel Activity and on Synaptic Transmission. Antioxidants & Redox Signaling 2005, 7: 1092-1100. PMID: 16115013, DOI: 10.1089/ars.2005.7.1092.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsApoptosisBcl-2-Associated X ProteinBcl-X ProteinCell MembraneElectrophysiologyIntracellular MembranesLiposomesLoligoMitochondriaMultigene FamilyNeurotransmitter AgentsPatch-Clamp TechniquesPeptidesPresynaptic TerminalsProtein Structure, TertiarySynapsesSynaptic TransmissionTime FactorsConceptsMitochondrial membraneBcl-2 family proteins BaxCell deathOuter mitochondrial membraneAction of BaxMitochondrial channel activityChannel activityNormal physiological settingsAntiapoptotic Bcl-xL proteinBcl-xL proteinDeath channelMitochondrial architectureMitochondrial channelsProapoptotic fragmentsLarge conductance channelPresynaptic terminalsBcl-xL.Proapoptotic proteinsAlternative functionsProtein BaxPhysiological settingsPhysiological roleSynaptic transmissionBaxNeurotransmitter release
2004
Exposure to Hypoxia Rapidly Induces Mitochondrial Channel Activity within a Living Synapse*
Jonas EA, Hickman JA, Hardwick JM, Kaczmarek LK. Exposure to Hypoxia Rapidly Induces Mitochondrial Channel Activity within a Living Synapse*. Journal Of Biological Chemistry 2004, 280: 4491-4497. PMID: 15561723, DOI: 10.1074/jbc.m410661200.Peer-Reviewed Original ResearchConceptsMitochondrial channel activityMitochondrial membraneChannel activityBcl-xLBcl-2 family proteinsPro-apoptotic fragmentsOuter mitochondrial membraneTrigger cell deathZ-VAD-FMKBenzyloxycarbonyl-VADFamily proteinsSynaptic responsesMulticonductance channelLarge conductance channelFluoromethyl ketoneCell deathMinutes of hypoxiaResponses of neuronsNeuronal functionSquid giant synapseSynaptic mitochondriaEarly eventsSynaptic functionHypoxic conditionsNeuronal deathProapoptotic N-truncated BCL-xL protein activates endogenous mitochondrial channels in living synaptic terminals
Jonas EA, Hickman JA, Chachar M, Polster BM, Brandt TA, Fannjiang Y, Ivanovska I, Basañez G, Kinnally KW, Zimmerberg J, Hardwick JM, Kaczmarek LK. Proapoptotic N-truncated BCL-xL protein activates endogenous mitochondrial channels in living synaptic terminals. Proceedings Of The National Academy Of Sciences Of The United States Of America 2004, 101: 13590-13595. PMID: 15342906, PMCID: PMC518799, DOI: 10.1073/pnas.0401372101.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsApoptosisBcl-X ProteinDecapodiformesElectric ConductivityEndopeptidasesHypoxiaIon ChannelsLiposomesMitochondriaNADPatch-Clamp TechniquesPorinsPresynaptic TerminalsProtein Processing, Post-TranslationalProto-Oncogene Proteins c-bcl-2Sequence DeletionVoltage-Dependent Anion ChannelsConceptsBcl-xLMitochondrial channelsDeath pathwaysMitochondrial membraneBcl-xL.Proapoptotic Bcl-2 family proteinsVoltage-dependent anion channelBcl-2 family proteinsOuter mitochondrial membraneCell death pathwaysHydrophobic C-terminusBcl-xL proteinAntiapoptotic Bcl-xLNeuronal death pathwaysDeath stimuliBH3 domainFamily proteinsSquid presynaptic terminalsMammalian cellsC-terminusAnion channelMitochondriaChannel activityOpposite effectHealthy neurons
1999
Prolonged Activation of Mitochondrial Conductances During Synaptic Transmission
Jonas E, Buchanan J, Kaczmarek L. Prolonged Activation of Mitochondrial Conductances During Synaptic Transmission. Science 1999, 286: 1347-1350. PMID: 10558987, DOI: 10.1126/science.286.5443.1347.Peer-Reviewed Original ResearchMeSH KeywordsAction PotentialsAnimalsCalciumCalcium ChannelsDecapodiformesElectric ConductivityElectric StimulationIntracellular MembranesIon ChannelsIon TransportMicroscopy, ElectronMitochondriaPatch-Clamp TechniquesPorinsPresynaptic TerminalsSynaptic TransmissionTime FactorsVoltage-Dependent Anion ChannelsConceptsChannel activityIon channel activityMitochondrial membraneOnly organellesIntracellular organellesIntact cellsIon channelsMitochondriaOrganellesLarge conductanceTens of secondsPresynaptic terminalsIon transportSynaptic transmissionSynaptic stimulationConductanceElectron microscopyPatch-clamp techniqueMembraneActivityCellsActivationSquidStimulation
1997
Giga-Ohm Seals on Intracellular Membranes: A Technique for Studying Intracellular Ion Channels in Intact Cells
Jonas E, Knox R, Kaczmarek L. Giga-Ohm Seals on Intracellular Membranes: A Technique for Studying Intracellular Ion Channels in Intact Cells. Neuron 1997, 19: 7-13. PMID: 9247259, DOI: 10.1016/s0896-6273(00)80343-8.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell MembraneCells, CulturedCHO CellsCricetinaeIon ChannelsPatch-Clamp TechniquesConceptsGiga-ohm sealsIntracellular membranesIntact cellsIntracellular ion channelsMembrane ion channel activityIon channel activityConventional patch clampingOrganelle membranesPlasma membraneInternal organellesInternal membranesInternal organelles membraneCell typesIon channelsChannel activityConfocal imagingInositol trisphosphateLipophilic fluorescent dyeMembranePatch clampingConcentric electrode arrangementPatch-clamp techniqueCellsIntact neuronsOrganelles